title: Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation.
abstract: We conducted a prospective cohort study testing the noninferiority of survival of ablative intravenous busulfan (IV-BU) vs ablative total body irradiation (TBI)-based regimens in myeloid malignancies. A total of 1483 patients undergoing transplantation for myeloid malignancies (IV-BU, N = 1025; TBI, N = 458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease, and disease stage at transplantation. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two-year probabilities of survival (95% confidence interval [CI]), were 56% (95% CI, 53%-60%) and 48% (95% CI, 43%-54%, P = .019) for IV-BU (relative risk, 0.82; 95% CI, 0.68-0.98, P = .03) and TBI, respectively. Corresponding incidences of transplant-related mortality (TRM) were 18% (95% CI, 16%-21%) and 19% (95% CI, 15%-23%, P = .75) and disease progression were 34% (95% CI, 31%-37%) and 39% (95% CI, 34%-44%, P = .08). The incidence of hepatic veno-occlusive disease (VOD) was 5% for IV-BU and 1% with TBI (P < .001). There were no differences in progression-free survival and graft-versus-host disease. Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM. These results support the use of myeloablative IV-BU vs TBI-based conditioning regimens for treatment of myeloid malignancies.
authors.affiliation: The University of Ottawa at the Ottawa Hospital Research Institute, Ottawa, ON, Canada;
authors.forename: Christopher
authors.initials: C
authors.lastname: Bredeson
authors.forename: Jennifer
authors.initials: J
authors.lastname: LeRademacher
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Kato
authors.forename: John F
authors.initials: JF
authors.lastname: Dipersio
authors.forename: Edward
authors.initials: E
authors.lastname: Agura
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Marcie R
authors.initials: MR
authors.lastname: Tomblyn
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhu
authors.forename: Philip L
authors.initials: PL
authors.lastname: McCarthy
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Armstrong
authors.forename: Angela
authors.initials: A
authors.lastname: Smith
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Rizzo
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Burkart
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Pasquini
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan